Introduction: Notch signaling is an evolutionarily conserved and widely used intercellular signaling pathway that influences cellular proliferation and differentiation. Most mammalian organs require Notch signaling during embryonic development and during tissue repair. In many tissues Notch signaling determines whether a cell remains in a replicating undifferentiated state or exits the cell cycle and terminally differentiates. My prior studies have demonstrated that the Notch receptor, Notch2, is required for the formation of epithelial structures in a variety of mouse organs including the kidney, liver, and heart. Research Goal: We plan to further study the role of Notch signaling during mammalian organogenesis and stem cell differentiation in hopes of obtaining information that is useful in the design and regulation of new cell therapy protocols. Approach: We have made mice that contain conditionally activated and conditionally inactivated alleles of Notch2. These mice will be used as tools for the study of the functional requirements of Notch2 in specific cell types in vivo. To allow the identification, characterization, and isolation of Notch2 expressing cells, we have also created ES cells that express Notch2-GFP and CMV-GFP transgenes.